Page 967 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

698 PART 5: Infectious Disorders

fluoroquinolone, trimethoprim-sulfamethoxazole, chloramphenicol, Europe, Australia, Kenya, Canada, and USA, many linked to travel and
and tetracycline resistant. some to hospitalization in India. Many of the isolates were urinary from
In the 1990s, a metallo-ß-lactamase termed IMP, emerged in Japan in patients with UTI or from those who had been catheterized. A large
the context of widespread use of imipenem and subsequently occurred proportion of the Indian isolates were from community-acquired infec-
26
sporadically worldwide but remained rare. Verona imipenemase (VIM), tions, especially UTI. A study of stool carriage at two Pakistani military
a new metallo-ß-lactamase, was first isolated in Europe from 1996, but hospitals showed NDM in 27% of inpatients and 13% of outpatients.
42
initially was confined to P aeruginosa. VIM-1–producing K pneumoniae Enterobacteriaceae isolated in 2009 from India showed that 28% were
was first reported extensively in 2002 in the ICUs of three Athens teach- CRE, half of which were NDM-1. 42,43 New Delhi metallo-ß-lactamase
ing hospitals and by the end of the decade had been reported from the is likely widespread in K pneumoniae and E coli in both hospitals and
majority of Greek hospitals, with 50% of K pneumoniae demonstrating community in India and Pakistan and has been reported from remote
carbapenem resistance in ICUs by 2007. Some Greek ICUs reported districts. 44,45 However, the absence of population-based surveillance
27
that few of their K pneumoniae isolates were susceptible to carbapenems. data and a National Reference Laboratory for resistant bacteria in both
28
The gene for this enzyme, bla VIM-1 , is on a plasmid, usually linked to other India and Pakistan means that uncertainty remains about the precise
resistance genes, including an ESBL and an aminoglycoside resistance epidemiology. In 2011, the extent to which these various forms of resis-
gene. Many isolates with bla VIM-1 were initially reported as susceptible to tance, especially NDM-1, will impact on both community- and hospital-
carbapenems by automated laboratory systems, leading to an underap- acquired UTIs throughout the world over the second decade of the
preciation of the Infection Control challenge. 21st century remains uncertain, but the negative potential is enormous.
In the USA, a single case of carbapenem-resistant Enterobacteriaceae
was reported first in 1991, due to a combination of AmpC hyperproduc- ■ ENTEROCOCCI AS URINARY PATHOGENS
tion with a porin mutation. A limited outbreak (eight cases, six deaths) of Enterococcus species are the third most frequent cause of CAUTI in the
29
carbapenem-resistant K pneumoniae by this mechanism was next reported
in a surgical ICU in New York City in 1999. This was superimposed on a ICU but are uncommonly a source of bacteremia and sepsis. A Spanish
prospective multicenter observational study of 21,979 ICU admissions
prolonged ESBL outbreak that had necessitated extensive use of imipenem 46
for empiric therapy. The outbreak was contained and terminated by vig- between 1997 and 2001 found enterococcal UTI in 0.15% of the total.
30
In ICUs the proportion of vancomycin-resistant enterococci (VRE),
orous Infection Control and limitation of cephalosporin use.
Klebsiella pneumoniae carbapenemase (KPC), a new nonmetallic mostly E faecium, is increasing but varies geographically. In many
ß-lactamase was first detected in North Carolina in 1999. The gene, countries, VRE has become endemic in hospitals, with a median ICU
31
bla KPC , is on a plasmid and most are part of a genetically distinct clone, colonization rate of 10% in the United States, with some units as high as
59%. In contrast VRE in France has only occurred in limited outbreaks,
47
sequence type (ST) 258. This is currently the main mechanism of
carbapenem resistance in the United States, concentrated in New York curtailed by effective Infection Control measures. Vancomycin-resistant
E faecium also commonly exhibits resistance to ampicillin and high-level
City and the North Eastern States. By 2010, KPCs had been reported 48
from 36 states, Washington DC, and Puerto Rico and had also spread aminoglycosides. A US tertiary center reported a rate of bacteriuria
due to VRE to be 23 per 10,000 admissions. Of 107 positive cultures,
worldwide, most extensively in Israel and Greece.
By 2010, KPCs were endemic in most Israeli and Greek hospitals, add- there were 13 symptomatic UTIs, two associated with bacteremia and
49
ing to the already established problem due to VIM-1 in Greece. 32-34 In one associated with death. Almost all VRE are susceptible to linezolid,
50
Israel, a National Infection Control response had reduced the number of daptomycin, nitrofurantoin, tigecycline, and chloramphenicol.
of both KPC and VIM have occurred throughout Europe, usually linked ■ ANTIMICROBIAL THERAPY
new KPC cases to 30 per month by 2010. Sporadic cases and outbreaks
to the larger Greek outbreak. 35,36 A hospital outbreak of KPC in Warsaw The choice of antimicrobial therapy for urosepsis raises a conflict
began in 2008 and was followed by extensive outbreaks throughout between the need to cover all possible pathogens and to avoid the
Poland. Klebsiella pneumoniae carbapenemases have also emerged in adverse effects of excessively broad-spectrum regimens. The impera-
35
various Latin American and Asian countries. Infections due to KPC tive of wise antimicrobial stewardship applies, tempered by the danger
and VIM-producing organisms are associated with a higher mortality that failure to provide therapy active against the subsequently identified
despite usually remaining susceptible to colistin and tigecycline. As a pathogen is associated with increased mortality, at least for patients
result of widespread use of colistin in Greek ICUs, colistin resistance with compromised host defense or septic shock. Studies of septic shock
has emerged, spread outside of Greece, and been associated with very associate delay in the administration of the first dose of effective antimi-
high mortality. 35,37,38 Isolates demonstrating resistance to all available crobial therapy with death, with each hour of delay causing an increment
agents, including colistin and tigecycline, have also been reported. 28,39 in mortality of almost 8% per hour over the first 6 hours. 51,52 If necessary,
Carbapenem-resistant K pneumoniae has followed the pathways of delay should be overcome by the physician administering the initial
patient referral, causing hospital outbreaks along the way, and has doses. Current local and international surveillance reports of resistance
remained largely a health care–associated pathogen, including CAUTI. in gram-negative bacilli should inform the choice of empiric therapy.
Interspecies transfer of bla KPC to E coli and other Enterobacteriaceae has A history of recent antimicrobial consumption or of international travel
occurred but not commonly and therefore organisms with KPCs are not involving hospitalization should also be taken into account. Two agents
yet significant community uropathogens. from different antimicrobial classes active against Enterobacteriaceae in
In 2008, the first of a new carbapenemase, termed New Delhi blood and urine are required, with subsequent tailoring of the regimen
metallo-β-lactamase (NDM-1), was identified in a urinary isolate of to a single agent with the narrowest spectrum, least toxicity and cost,
K pneumoniae in Sweden. The patient had recently returned from based on the results of cultures.
India with a urinary catheter following extensive hospitalization. An Historically, a combination of an aminoglycoside and ampicillin
E coli with the same NDM-1 was subsequently found in his stool, consis- provided cost-effective, empiric therapy for pyelonephritis in the com-
tent with interspecies transfer. In 2010, a landmark report of NDM-1 munity. However, because 30% to 80% of E coli urinary isolates are now
40
isolates from throughout the United Kingdom and Indian subcontinent resistant, ampicillin can no longer be recommended. The addition of a
identified 180 isolates with NDM-1, mostly K pneumoniae or E coli, β-lactamase inhibitor, such as clavulanic acid or sulbactam, eliminates
37 from the United Kingdom, and the rest from 20 different centers in most resistance, but not that due to ESBL or CRE. Ampicillin-sulbactam
India, Pakistan, and Bangladesh. At least 17 of the UK patients had or clavulanic acid (available intravenously in many countries but not in
41
traveled to India or Pakistan over the previous year, 14 of who were the United States) combined with an aminoglycoside is an appropriate
hospitalized there. Subsequent reports emerged from elsewhere in Asia, choice in regions in which ESBL prevalence remains low (Table 75-2).

section05_c74-81.indd 698 1/23/2015 12:37:26 PM